Transplantation of normal liver cells as a free graft is being investigated as therapy in two animal models of congenital enzyme deficiency disease: a. jaundiced uridine diphosphate glucuronyl transferase (UDPGT) deficient Gunn rats; and b. the actalasemic (Csb) mouse. In the latter model, transplantation of bone marrow cells from normal catalasemic (Csa) mice is being evaluated for its ability to raise blood catalase levels of Csb mice. Transplantation of liver cells is also being performed to provide metabolic support in animals with acute hepatic failure. Liver failure is induced in rats with dimethylnitrosamine (DMNA) or D-galactosamine (D-GI), and liver cells are transplanted intraperitoneally or via the portal vein. The investigations performed so far show that liver cells from heterozygous Gunn rats with normal UDPGT activity can lower the bilirubin of UDPGT deficient homozygous Gunn rats, but normal values are not consistently achieved. Transplantation of Csa liver cells to Csb acatalasemic mice does not raise blood catalase levels, but Csa bone marrow transplants are effective. Isologous, allogenic, and xenogeneic hepatocytes increase the survival of rats with DMNA induced hepatic failure. During the coming year we will transplant Gunn rats with an increased number of liver cells, correlate plasma bilirubin levels and UDPGT activity in the liver before and following transplantation, and determine whether the partial hepatectomy before transplantation will facilitate the survival of grafted liver cells. In acatalasemic mice, liver catalase levels will be measured after liver cell transplantation via the spleen. Acatalasemic mice will receive bone marrow transplants from allogeneic donors. The effect of liver cell transplantation will be determined in rats and dogs with acute hepatic failure induced by D-galactosamine, an hepatotoxin that induces a spectrum of biochemical abnormalities akin to clinical acute hepatic failure syndrome.